A Fixed Dose Study of Ropinirole Prolonged Release as Adjunctive Treatment in Patients With Advanced Parkinson's Disease (TANDEM-569)

A Fixed Dose, Dose-response Study of Ropinirole Prolonged Release (PR) as Adjunctive Treatment to L-dopa in Patients With Advanced Parkinson's Disease

This is a double blind, fixed dose, parallel group study to characterize the dose response of ropinirole PR as adjunctive therapy to L-dopa in patients with late stage Parkinson's disease. The primary endpoint of this study, mean change from baseline in total awake time spent "off' is the same endpoint as used in the ropinirole PR pivotal study for advanced Parkinson's disease patients. This study includes a wide range of ropinirole doses (4-24mg) with the 8mg, 12mg, and 16mg per day doses powered to detect a 1.7 hour difference in total awake time spent "off" compared with placebo. The dose of Ldopa will remain stable through the study, unless the subject experiences tolerability issues that require an L-dopa dose reduction. Up to three L-dopa dose reductions are allowed, making a total reduction of up to approximately 30%. Keeping the L-dopa dose constant where possible is important to avoid confounding the efficacy data. Clinical review of the primary and secondary endpoints will be performed in order to establish the lowest maximally effective therapeutic dose.

Study Overview

• Status: Completed
• Conditions: Parkinson Disease
• Intervention / Treatment: Drug: ropinirole/L-dopa; Drug: placebo/L-dopa

• Study Type: Interventional
• Enrollment (Actual): 352
• Phase: Phase 4

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, B1602DBG
    • GSK Investigational Site
  • Buenos Aires, Argentina, C1426AHA
    • GSK Investigational Site
  • Caba, Argentina, 1209
    • GSK Investigational Site
  • Ciudad Autónoma de Buenos Aires, Argentina, C1133AAW
    • GSK Investigational Site
  • Buenos Aires
    • Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1200AAT
      • GSK Investigational Site
    • Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1419AHN
      • GSK Investigational Site
    • Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina, C1192AAW
      • GSK Investigational Site
    • San Martin, Buenos Aires, Argentina, 1650
      • GSK Investigational Site
• Chile
  • Santiago, Chile, 7500551
    • GSK Investigational Site
  • Santiago, Chile, 7500710
    • GSK Investigational Site
  • Santiago, Chile, 8260094
    • GSK Investigational Site
  • Región De Los Lagos
    • Valdivia, Región De Los Lagos, Chile, 5090145
      • GSK Investigational Site
  • Valparaíso
    • Viña del Mar, Valparaíso, Chile, 2570017
      • GSK Investigational Site
• Estonia
  • Tallinn, Estonia, 10617
    • GSK Investigational Site
  • Tallinn, Estonia, 10138
    • GSK Investigational Site
• Korea, Republic of
  • Anyang-Si, Korea, Republic of, 431-070
    • GSK Investigational Site
  • Busan, Korea, Republic of, 602-715
    • GSK Investigational Site
  • Daejeon, Korea, Republic of, 371718
    • GSK Investigational Site
  • Seongnam-si Gyeonggi-do, Korea, Republic of, 463-707
    • GSK Investigational Site
  • Seoul, Korea, Republic of, 138-736
    • GSK Investigational Site
  • Seoul, Korea, Republic of, 152-703
    • GSK Investigational Site
  • Seoul, Korea, Republic of, 130-702
    • GSK Investigational Site
  • Sungnam, Korea, Republic of, 463712
    • GSK Investigational Site
• Russian Federation
  • Chelyabinsk, Russian Federation, 454136
    • GSK Investigational Site
  • Ekaterinburg, Russian Federation, 620102
    • GSK Investigational Site
  • Kazan, Russian Federation, 420012
    • GSK Investigational Site
  • Krasnoyarsk, Russian Federation, 660022
    • GSK Investigational Site
  • Kursk, Russian Federation, 305007
    • GSK Investigational Site
  • Novosibirsk, Russian Federation, 630091
    • GSK Investigational Site
  • Omsk, Russian Federation, 644033
    • GSK Investigational Site
  • Perm, Russian Federation, 614990
    • GSK Investigational Site
  • Saratov, Russian Federation, 410012
    • GSK Investigational Site
  • Smolensk, Russian Federation, 214019
    • GSK Investigational Site
  • St.Petersburg, Russian Federation, 194044
    • GSK Investigational Site
  • Ufa, Russian Federation, 450000
    • GSK Investigational Site
  • Yaroslavl, Russian Federation, 150030
    • GSK Investigational Site
• Slovakia
  • Banska Bystrica, Slovakia, 974 04
    • GSK Investigational Site
  • Bratislava, Slovakia, 826 06
    • GSK Investigational Site
  • Bratislava, Slovakia, 813 69
    • GSK Investigational Site
  • Bratislava, Slovakia, 833 05
    • GSK Investigational Site
  • Bratislava, Slovakia, 831 03
    • GSK Investigational Site
  • Dubnica Nad Vahom 1, Slovakia, 1841
    • GSK Investigational Site
  • Trnava, Slovakia, 91702
    • GSK Investigational Site
• United States
  • California
    • Fountain Valley, California, United States, 92708
      • GSK Investigational Site
    • Pasadena, California, United States, 91105
      • GSK Investigational Site
    • Reseda, California, United States, 91355
      • GSK Investigational Site
    • Ventura, California, United States, 93003
      • GSK Investigational Site
  • Florida
    • Boca Raton, Florida, United States, 33486
      • GSK Investigational Site
    • Tampa, Florida, United States, 33612
      • GSK Investigational Site
  • Massachusetts
    • Springfield, Massachusetts, United States, 01104
      • GSK Investigational Site
  • New York
    • Forest Hills, New York, United States, 11375
      • GSK Investigational Site
  • Virginia
    • Richmond, Virginia, United States, 23249
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of idiopathic Parkinson's disease (according to modified Hoehn & Yahr criteria Stages II-IV) and demonstrating lack of control with L-dopa therapy (e.g.

end of dose akinesia, simple on/off fluctuations).

• Subjects receiving a stable dose of L-dopa for at least 4 weeks prior to screening.
• A minimum of 3 hours awake "off-time" for each diary day recorded during the baseline period.
• Men or non-pregnant/non-breast-feeding women of at least 30 years of age at screening. Women of child-bearing potential must be practicing a clinically accepted method of contraception during the study and for at least one month prior to randomization and one month following completion of the study. Acceptable contraceptive methods include abstinence, oral contraception, injectable progestogen, implants of levonorgestrel, estrogenic vaginal ring, percutaneous contraceptive patches, surgical sterilisation, male partner sterilization, intrauterine device [IUD], or double barrier method: condom or occlusive cap (diaphragm or cervical/vault caps) plus spermicidal agent (foam/gel/film/cream/suppository.
• Provide written informed consent for this study.
• Be willing and able to comply with study procedures, including diary card completion and follow-up clinic visits.

Exclusion Criteria:

• Late stage advanced subjects demonstrating incapacitating peak dose or diphasic dyskinesia on their stable dose of L-dopa
• Consumption of any dopamine agonist, including ropinirole, within four weeks of randomization in the study.
• Subjects with severe, clinically significant condition(s) other than Parkinson's disease which, in the opinion of the investigator, would render the subject unsuitable for the study (e.g., psychiatric, haematological, renal, hepatic, endocrinology, neurological [other than Parkinson's disease], cardiovascular, or active malignancy [other than basal cell carcinoma]).
• Subjects with crippling degenerative arthritis or other physical or mental conditions which would preclude accurate assessment of efficacy or safety.
• Subjects with prior or current major psychosis (e.g., schizophrenia or psychotic depression) e.g. scoring 3 or 4 on UPDRS item 2 [thought disorder] or item 3 [depression].
• Subjects with severe clinical dementia e.g. scoring 3 or 4 on UPDRS item 1 [mentation].
• Subjects with severe dizziness or fainting due to postural hypotension on standing.
• Subjects with a personal history of melanoma.
• Subjects with clinically significant abnormalities in laboratory or ECG tests at Screening. If findings are outside the normal range and the subject is included, it must be documented by the investigator that the findings are not of clinical significance.
• Subjects who are diagnosed with an impulse control disorder. The modified MIDI will be conducted at screening. Subjects who score positive for this screen must be referred to a specialist for diagnostic evaluation.
• Subjects who have an active suicidal plan/intent or have had active suicidal thoughts in the past 6 months. Subjects who have a history of suicide attempt in the last 2 years or more than 1 lifetime suicide attempt.
• Current alcohol or drug dependence.
• Definite or suspected personal or family history of clinically significant adverse reactions or hypersensitivity to ropinirole (or to drugs with a similar chemical structure) that would preclude long-term dosing with ropinirole.
• Withdrawal, introduction, or change in dose of hormone replacement therapy and/or any drug known to substantially inhibit CYP1A2 (e.g. ciprofloxacine, fluvoxamine, cimetidine, ethinyloestradiol) or induce CYP1A2 (e.g. tobacco, omeprazole) within 7 days prior to enrolment (randomization). Subjects already on chronic therapy with any of these agents may be enrolled but doses must have remained stable from 7 days prior to enrolment (randomization) through the end of the treatment period.
• Women who are pregnant or breast-feeding.
• Use of an investigational drug from 30 days or 5 half-lives (whichever is longer) prior to enrolment (randomization) through to the end of the treatment period. 15. Women who are pregnant or breast-feeding. 16. Use of an investigational drug from 30 days or 5 half-lives (whichever is longer) prior to enrolment (randomization) through to the end of the treatment period.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: ropinirole; active treatment 4, 8, 12, 16, or 24mg/day	Drug: ropinirole/L-dopa; Ropinirole as adjunctive therapy with L-dopa
PLACEBO_COMPARATOR: placebo; placebo comparator 4, 8, 12, 16, or 24mg/day	Drug: placebo/L-dopa; Placebo as adjunctive therapy with L-dopa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline (BL) in Total Awake Time Spent "Off" at Week 4 of Maintenance Period	"Off" time is defined as the state in which the participants(par) symptoms include lack of mobility(bradykinesia) with or without additional features such as tremor or rigidity. Par were asked to record awake time "off ", awake time "on", troublesome dyskinesias(TD) during awake time "on", or time asleep for 30 minute intervals in 24 hr diary cards for 2 days preceding visits. Total number of awake hrs spent "off" per 24-hr period was the average of the 2 diary cards of the sum of awake hours spent "off" in each 24-hr diary card. BL is the last non-missing assessment measured on or before the first dose, change from BL was calculated by subtracting the BL values from the MP Week 4 values. Mixed Model Repeated Measures (MMRM) model used BL total awake time 'Off', treatment, visit and treatment by visit	Baseline and Week 4 of the Maintenance Period (Study Week 17)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Responder Rate Defined as the Percentage of Participants With a 20% Reduction in Baseline (BL) "Off" Time at Week-4 of Maintenance Period	The responder rate was defined as the percentage of par with greater than or equal to (>=) 20 percent (%) reduction in their individual BL "off" time at Week 4 of the Maintenance Period. The "off" time is defined as the state in which the participants' symptoms include lack of mobility (bradykinesia) with or without additional features such as tremor or rigidity. BL is defined as the last non-missing assessment measured on or before the first dose date. Responder Rate (Least Squares [LS] means on inverse linked scale), odds ratio with 95% CI and p-value comparing against placebo were estimated by Generalized Estimating Equations (GEE) model. Baseline total awake time 'Off', treatment, visit and treatment*visit are included in the model.	Week 4 of the Maintenance Period (Study Week 17)
Percentage of Participants With a >=1 Hour Reduction in Baseline "Off" Time at Week 4 of the Maintenance Period	The "off" time is defined as the state in which the participants' symptoms include lack of mobility (bradykinesia) with or without additional features such as tremor or rigidity. BL is defined as the last non-missing assessment measured on or before the first dose date. The percent change from BL was calculated by subtracting the BL values from the Maintenance Period Week 4 values. Percentage of participants meeting the criterion (LS mean on inverse linked scale), odds ratio with 95% CI and p-value comparing against placebo were estimated by Generalized Estimating Equations (GEE) model. Baseline 'off-time', treatment, visit and treatment*visit are included in the model.	Baseline and Week 4 of the Maintenance Period (Study Week 17)
Percentage of Participants With a >=2 Hours Reduction in Baseline "Off" Time at Week 4 of the Maintenance Period	The "off" time is defined as the state in which the participants' symptoms include lack of mobility (bradykinesia) with or without additional features such as tremor or rigidity. BL is defined as the last non-missing assessment measured on or before the first dose date. The percent change from BL was calculated by subtracting the BL values from the Maintenance Period Week 4 values. Percentage of participants meeting the criterion (LS mean on inverse linked scale), odds ratio with 95% CI and p-value comparing against placebo were estimated by Generalized Estimating Equations (GEE) model. Baseline 'off-time', treatment, visit and treatment*visit are included in the model.	Baseline and Week 4 of the Maintenance Period (Study Week 17)
Responder Rate According to the Clinical Global Impression-global Improvement (CGI-I) Scale at Week 4 of the Maintenance Period	The CGI-I scale allows the investigator to rate the participant's total improvement since the beginning of treatment (Baseline). Baseline is defined as the last non-missing assessment measured on or before the first dose date. The scale is rated from 1-7 where 1 = "very much improved", 2 = "much improved", 3 = "minimally improved", 4 = "no change", 5 = "minimally worse, 6 = "much worse", and 7 = "very much worse". The responder rate is defined as the percentage of participants with a score of 1 or 2. The Generalized Estimating Equations (GEE) model was used to determine CGI responder rate with treatment, visit, and treatment by visit interaction included in the model. Only scheduled visits were included.	Week 4 of the Maintenance Period (Study Week 17)
Change From Baseline in Absolute Awake Time Spent "on" Without Troublesome Dyskinesia (TD) at Week 4 of the Maintenance Period	Dyskinesias are involuntary twisting, turning movements caused by medication during "on" time in Parkinson's Disease (PD). TD is defined as those movements that interfere with function and cause meaningful discomfort. Par were asked to record awake time "off", awake time "on", TD during awake time "on", or time asleep for all 30 minute time intervals in 24 hour diary cards for the 2 days preceding each visit. The total number of awake hours spent "on" without TD per 24-hour period was the average across the 2 diary cards of the sum of awake hours spent "on" without TD in each 24 hour diary card. The change from BL was calculated by subtracting the BL values from the MP Week 4 values. LS means, 95% CIs and P-values were estimated from Mixed Model Repeated Measures (MMRM). Par with a non-missing efficacy observation at BL and during the MP were analyzed.	Baseline and Week 4 of the Maintenance Period (Study Week 17)
Change From Baseline in Absolute Awake Time Spent "on" at Week 4 of the Maintenance Period	Par were asked to record awake time "off", awake time "on", TD during awake time "on", or time asleep for all 30 minute time intervals in 24 hour diary cards for the 2 days preceding each visit of the study. The total number of awake hours spent "on" per 24-hour period was the average across the 2 diary cards of the sum of the awake hours spent "on" in each 24 hour diary card. BL is defined as the last non-missing assessment measured on or before the first dose date. The change from BL was calculated by subtracting the BL values from the Maintenance Period Week 4 values. LS means, 95% CIs and P-values were estimated from MMRM.	Baseline and Week 4 of the Maintenance Period (Study Week 17)
Change From Baseline for Total Sleep Time During the Night Time Hours of Sleep at Week 4 of the Maintenance Period	Par. were asked to record awake time "off", awake time "on", TD during awake time "on", or time asleep for all 30 minute time intervals in 24 hour diary cards for the 2 days preceding each visit of the study. The total sleep hours during the night time hours of sleep was the average across the 2 diary cards of the sum of time (hours) asleep during night time in each 24-hour diary card. BL is defined as the last non-missing assessment measured on or before the first dose date. The change from BL was calculated by subtracting the BL values from the Maintenance Period Week 4 values. LS means, 95% CIs and P-values were estimated from MMRM.	Baseline and Week 4 of the Maintenance Period (Study Week 17)
Percent Change From Baseline in Awake Time Spent "Off" at Week 4 of the Maintenance Period	The "off" state is defined as the state in which the participants' symptoms include lack of mobility (bradykinesia), with or without additional features such as tremor or rigidity. Par. were asked to record awake time "off", awake time "on", TD during awake time "on", or time asleep for all 30 minute time intervals in 24 hour diary cards for the 2 days preceding each visit of the study. The total number of awake hours spent "off" per 24-hour period was the average across the 2 diary cards of the sum of awake hours spent "off" in each 24-hour diary card. The percent change from BL was calculated by subtracting the BL values from the Maintenance Period Week 4 values divided by BL values multiplied (×) the results with 100. LS means, 95% CIs and P-values were estimated from MMRM.	Baseline and Week 4 of the Maintenance Period (Study Week 17)
Percent Change From Baseline in Awake Time Spent "on" Without TD at Week 4 of the Maintenance Period	Dyskinesias are involuntary twisting, turning movements caused by medication during "on" time in PD. TD is defined as those movements that interfere with function and cause meaningful discomfort. Par. were asked to record awake time "off", awake time "on", TD during awake time "on", or time asleep for all 30 minute time intervals in 24 hour diary cards for the 2 days preceding each visit of the study. The total number of awake hours spent "on" without TD per 24-hour period was the average across the 2 diary cards of the sum of awake hours spent "on" without TD in each 24-hour diary card. The percent change from BL was calculated by subtracting the BL values from the Maintenance Period Week 4 values divided by BL values × 100. LS means, 95% CIs and P-values were estimated from MMRM.	Baseline and Week 4 of the Maintenance Period (Study Week 17)
Percent Change From Baseline in Awake Time Spent "on" at Week 4 of the Maintenance Period	Par. were asked to recordawake time "off", awake time "on", TD during awake time "on", or time asleep for all 30 minute time intervals in 24 hour diary cards for the 2 days preceding each visit of the study. The total number of awake hours spent "on" per 24-hour period was the average across the 2 diary cards of the sum of awake hours spent "on" in each 24-hour diary card. The percent change from BL was calculated by subtracting the BL values from the Maintenance Period Week 4 values divided by BL values × 100. LS means, 95% CIs and P-values were estimated from MMRM.	Baseline and Week 4 of the Maintenance Period (Study Week 17)
Percent Change From Baseline in Total Sleep Time During the Night Time Hours of Sleep, at Week 4 of the Maintenance Period	Par. were asked to record awake time "off", awake time "on", TD during awake time "on", or time asleep for all 30 minute time intervals in 24 hour diary cards for the 2 days preceding each visit of the study. The total sleep hours during the night time hours of sleep was the average across the 2 diary cards of the sum of time (hours) asleep during night time in each 24-hour diary card. BL is defined as the last non-missing assessment measured on or before the first dose date. The percent change from BL was calculated by subtracting the BL values from the Maintenance Period Week 4 values divided by BL value × 100. LS means, 95% CIs and P-values were estimated from MMRM.	Baseline and Week 4 of the Maintenance Period (Study Week 17)
Change From Baseline in the Percent Awake Time Spent "Off" at Week 4 of the Maintenance Period	The "off" state is defined as the state in which the participants' symptoms include lack of mobility(bradykinesia), with or without additional features such as tremor or rigidity. Par were asked to record awake time "off", awake time "on", TD during awake time "on", or time asleep for all 30 minute time intervals in 24 hour diary cards for the 2 days preceding each visit of the study. The total number of awake hours spent "off" per 24-hour period was the average across the 2 diary cards of the sum of awake hours spent "off" in each 24-hour diary card. The percentage of awake time spent "off"= Awake time spent "off" divided by (Awake time spent "off" + Awake time spent "on") × 100. BL is defined as the last non-missing assessment measured on or before the first dose date. The change from BL was calculated by subtracting the BL values from the MP Week 4 values. LS means, 95% CIs and P-values were estimated from MMRM.	Baseline and Week 4 of the Maintenance Period (Study Week 17)
Change From Baseline in the Percent Awake Time Spent "on" Without TD at Week 4 of the Maintenance Period	Dyskinesias are involuntary twisting, turning movements caused by medication during "on" time in PD. TD is defined as those movements that interfere with function and cause meaningful discomfort. Par were asked to record awake time "off", awake time "on", TD during awake time "on", or time asleep for all 30 minute time intervals in 24 hr diary cards for the 2 days preceding each visit of the study. The total number of awake hr spent "on" without TD per 24-hr period was the average across the 2 diary cards of the sum of awake hr spent "on" without TD in each 24-hr diary card. Percentage of awake time spent "on"without TD= Awake time spent "on" without TD divided by(Awake time spent "on" + Awake time spent "off") × 100. BL is defined as the last non-missing assessment measured on or before the first dose date, change from BL was calculated by subtracting BL values from MP Week 4 values. LS means, 95% CIs and P-values were estimated from MMRM.	Baseline and Week 4 of the Maintenance Period (Study Week 17)
Change From Baseline in the Percent Awake Time Spent "on" at Week 4 of the Maintenance Period	Par. were asked to record awake time "off", awake time "on", TD during awake time "on", or time asleep for all 30 minute time intervals in 24 hour diary cards for the 2 days preceding each visit of the study. The total number of awake hours spent "on" per 24-hour period was the average across the 2 diary cards of the sum of awake hours spent "on" in each 24-hour diary card. The percentage of awake time spent "on"= Awake time spent "on" divided by (Awake time spent "on" + Awake time spent "off") × 100. BL is defined as the last non-missing assessment measured on or before the first dose date. The change from BL was calculated by subtracting the BL values from the Maintenance Period Week 4 values. LS means, 95% CIs and P-values were estimated from MMRM.	Baseline and Week 4 of the Maintenance Period (Study Week 17)
Change From Baseline in the Percent of a 24-hour Day Spent "Off" at Week 4 of the Maintenance Period	The "off" state is defined as the state in which the participants' symptoms include lack of mobility (bradykinesia), with or without additional features such as tremor or rigidity. Par were asked to record awake time "off", awake time "on", TD during awake time "on", or time asleep for all 30 minute time intervals in 24 hour diary cards for the 2 days preceding each visit of the study. The total number of day awake hours spent "off" per 24-hour period was the average across the 2 diary cards of the sum of awake hours spent "off" in each 24-hour diary card. The percentage of 24 hour day spent "off"= awake time spent "off" divided by 24 x 100. BL is defined as the last non-missing assessment measured on or before the first dose date. The change from BL was calculated by subtracting the BL values from the MP Week 4 values. LS means, 95% CIs and P-values were estimated from MMRM.	Baseline and Week 4 of the Maintenance Period (Study Week 17)
Change From Baseline in the Percent of a 24- Hour Day Spent "on" Without TD at Week 4 of the Maintenance Period	Dyskinesias are involuntary twisting, turning movements caused by medication during "on" time in PD. TD is defined as those movements that interfere with function and cause meaningful discomfort. Par were asked to record awake time "off", awake time "on", TD during awake time "on", or time asleep for all 30 minute time intervals in 24 hr diary cards for the 2 days preceding each visit. The total number of day awake hr spent "on" without TD per 24-hr period was the average across the 2 diary cards of the sum of awake hours spent "on" without TD in each 24-hour diary card. The percentage of 24 hr day spent "on" without TD= awake time spent "on" without TD divided by 24 × 100. BL is defined as the last non-missing assessment measured on or before the first dose date, change from BL was calculated by subtracting the BL values from the MP Week 4 values. LS means, 95% CIs and P-values were estimated from MMRM.	Baseline and Week 4 of the Maintenance Period (Study Week 17)
Change From Baseline in the Percent of a 24-hour Day Spent "on" at Week 4 of the Maintenance Period	Par. were asked to record awake time "off", awake time "on", TD during awake time "on", or time asleep for all 30 minute time intervals in 24 hour diary cards for the 2 days preceding each visit of the study. The total number of day awake hours spent "on" per 24-hour period was the average across the 2 diary cards of the sum of awake hours spent "on" in each 24-hour diary card. The percentage of a 24-hour day spent "on" = Awake time spent "on" divided by 24 × 100. BL is defined as the last non-missing assessment measured on or before the first dose date. The change from BL was calculated by subtracting the BL values from the Maintenance Period Week 4 values. LS means, 95% CIs and P-values were estimated from MMRM.	Baseline and Week 4 of the Maintenance Period (Study Week 17)
Change From Baseline in Total Sleep Time During the Night Time Hours of Sleep as a Percentage of a 24-hour Day, at Week 4 of the Maintenance Period	Par were asked to record awake time "off", awake time "on", TD during awake time "on", or time asleep for all 30 minute time intervals in 24 hour diary cards for the 2 days preceding each visit of the study. The total sleep hours during the night time hours of sleep was the average across the 2 diary cards of the sum of time (hours) asleep during night time in each 24-hour diary card. The percentage of a 24-hour day spent asleep during the night time hours = Total sleep hours during the night time hours of sleep divided by 24 × 100. BL is defined as the last non-missing assessment measured on or before the first dose date. The change from BL was calculated by subtracting the BL values from the Maintenance Period Week 4 values. LS means, 95% CIs and P-values were estimated from MMRM.	Baseline and Week 4 of the Maintenance Period (Study Week 17)
Change From Baseline in Unified Parkinson Disease Rating Scale (UPDRS) Motor Score With Participants in an "on" State, at Week 4 of the Maintenance Period	The UPDRS is a clinician based rating scale used to measure motor impairments and disability. The UPDRS assesses six features of PD impairment. These are evaluated using a combination of data collected by interview and examination of the par.. One of the six features include the Part III-motor examination where scores can range 0 to 108 with par. in an "on" state where the maximum score indicates the worse condition. BL is defined as the last non-missing assessment measured on or before the first dose date. The change from BL was calculated by subtracting the BL values from the Maintenance Period Week 4 values. LS means, 95% CIs and P-values were estimated from MMRM.	Baseline and Week 4 of the Maintenance Period (Study Week 17)
Change From Baseline in UPDRS Activities of Daily Living (ADL) Score With Participants in an "on" State, at Week 4 of the Maintenance Period	The UPDRS Part II is the ADL score and can range from 0 to 52 as determined by the physician. The higher score indicates the worse condition. Test were performed when the par. is in the "on" state of PD. BL is defined as the last non-missing assessment measured on or before the first dose date. The change from BL was calculated by subtracting the BL values from the Maintenance Period Week 4 values. LS means, 95% CIs and P-values were estimated from MMRM.	Baseline and Week 4 of the Maintenance Period (Study Week 17)
Change From Baseline in UPDRS ADL Score With Participants in an "Off" State, at Week 4 of the Maintenance Period	The UPDRS Part II is the ADL score and can range from 0 to 52 as determined by the physician. The higher score indicates the worse condition. Test was performed when the par is in the "off" state of PD. The "off" time is defined as the state in which the participants' symptoms include lack of mobility (bradykinesia) with or without additional features such as tremor or rigidity. BL is defined as the last non-missing assessment measured on or before the first dose date. The change from BL was calculated by subtracting the BL values from the Maintenance Period Week 4 values. LS means, 95% CIs and P-values were estimated from MMRM.	Baseline and Week 4 of the Maintenance Period (Study Week 17)
Change From Baseline in UPDRS Part I at Week 4 of the Maintenance Period	The UPDRS Part I scores mentation, behavior and mood as determined by a physician and par. were tested during the "on" phase of PD. This component of the UPDRS is the total score for 4 items (the items 1 to 4 include intellectual impairment, thought disorder, motivation / initiative, and depression) and may have a value ranging from 0 to 16 as determined by a physician. The higher score (16) indicates the maximum score and the worse condition. All 4 items have to be present for a total score to be calculated. If one or more items are missing, the total score for the component would also be missing. BL is defined as the last non-missing assessment measured on or before the first dose date. The change from BL was calculated by subtracting the BL values from the individual post-randomization values. LS means, 95% CIs and P-values were estimated from MMRM.	Baseline (BL) and Week 4 of the Maintenance Period (Study Week 17)
Percentage of Participants Withdrawn From the Study Due to Lack of Efficacy	The percentage of participants who withdrew from the study due to lack of efficacy as defined by either the participant or the investigator is presented here. All participants with a non-missing efficacy observation at Baseline and at least one post-Baseline efficacy assessment at any time during the study were analyzed.	From start of study treatment until end of treatment (assessed up to 18 weeks)

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 2, 2012
• Primary Completion (ACTUAL): November 18, 2014
• Study Completion (ACTUAL): November 18, 2014

Study Registration Dates

• First Submitted: December 1, 2011
• First Submitted That Met QC Criteria: December 15, 2011
• First Posted (ESTIMATE): December 19, 2011

Study Record Updates

• Last Update Posted (ACTUAL): June 20, 2018
• Last Update Submitted That Met QC Criteria: June 18, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Dopamine Agonists; Dopamine Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Levodopa; Ropinirole; Dihydroxyphenylalanine
• Other Study ID Numbers: 111569

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Study Protocol
   Information identifier: 111569
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Individual Participant Data Set
   Information identifier: 111569
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Dataset Specification
   Information identifier: 111569
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Informed Consent Form
   Information identifier: 111569
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Clinical Study Report
   Information identifier: 111569
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Statistical Analysis Plan
   Information identifier: 111569
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register